Major life events such as divorce, death of a spouse or a child, or long-term unemployment are stressful to most people and animal models have suggested a link between stress and onset of parkinsonian symptoms. In a large case-control study based on nationwide registries, we aim to address whether major life events are risk factors for Parkinson's disease. Between 1986 and 2006, we identified 13,695 patients with a (PD) primary diagnosis of PD in the Danish National Hospital Register. Each case was frequency matched by age and gender to five population controls. Information on major life events before onset of PD was ascertained from national registries. Among men, number of life events was associated with risk of Parkinson's disease in an inverse dose-response manner (P <0.0001). Compared to no events, three or more events were associated with a 42% lower risk of PD (OR = 0.58; 95 % CI: 0.34-0.99). Life events were not associated with PD in women. In contrast, a higher risk of PD was observed among women who had never been married (1.16; 1.04-1.29) and among men (1.47; 1.18-1.82) and women (1.30; 1.05-1.61) who have never been employees. The lower risk of Parkinson's disease among men who had experienced life events was unexpected but might suggest a general "risk avoidance behavior" in Parkinson's patients.